This proposal is to request support for a Keystone Symposia meeting entitled "PI 3-Kinase Signaling in Disease", organized by Peter M. Finan, Jean Zhao and Lewis C. Cantley, which will be held in Olympic Valley, California from April 22 - 27, 2009. The PI 3-kinase signaling pathway controls multiple physiological processes including cell growth, cell proliferation and cell movement. Dysregulation of this pathway in cancer, inflammation and heart disease has led to the emergence of PI 3-kinase as a promising therapeutic target. This meeting aims to bring together scientists and clinicians from academia and industry to discuss the opportunities and liabilities of targeting the PI 3-kinase pathway in disease, drawing on human pathophysiology and genetics, mouse models and preclinical data with new PI 3-kinase inhibitors. Of particular relevance to the field of cancer therapeutics will be the discussion of clinical data from inhibitors of the PI3K / mTOR pathway and the best path forward for the development of pathway modulators in cancer (keynote lecture and 2 half day sessions). In addition, the basic mechanisms by which the pathway is dysregulated in cancer will be discussed on multiple days. Opportunities for interdisciplinary interactions will be further enhanced by the concurrent meeting "Complex Lipids in Biology: Signaling, Compartmentalization and Disease", which will share a session with this meeting. Public Health Relevance: This symposium will focus on the PI 3-Kinase (PI3K) signaling pathway which is rapidly emerging as a promising therapeutic target in a number of human disease indications including cancer, metabolic disorders, inflammation and heart disease. The aim of the meeting is to assemble experts in basic research, translational medicine and drug discovery for critical discussion of recent advances regarding PI3K signaling, both from the point of view of basic biology and progress towards developing pharmaceutical modulators of the PI3K.